The OPTIC NERVE is a bundle of nerve fibres that conducts visual messages from the eye into the brain. In the centre of most optic nerves is a depression known as the optic nerve “cup”. The portion of the optic nerve visible to the ophthalmologist is only a very short section of the nerve. Most of the optic nerve is located behind the eyeball, and cannot be seen without a CT or MRI scan. The most common optic nerve disorders (optic neuropathies) not due to trauma include glaucoma, optic neuritis, pseudotumor cerebri, non-arteritic ischemic optic neuropathy and arteritic ischemic optic neuropathy (giant cell arteritis).
OPEN ANGLE GLAUCOMA is a chronic, painless process, and patients may not realize they have it until it is too late. Early in the disease the peripheral vision is lost. The central vision that we use to see faces and read books, is preserved until late in the disease. An eye pressure higher than the optic nerve can withstand, compromised blood supply and “pre-programmed” cell death are felt to be some of the causes for glaucoma. Increased pressure causes some of the optic nerve fibres to die. Because there are less fibres at the rim of the optic nerve, the cup of the optic nerve appears to enlarge in glaucoma. Glaucoma eye drops, laser and glaucoma surgery can help control the eye pressure. Neuroprotective agents are being investigated.
Not all patients with glaucoma have high eye pressure, making it potentially difficult to distinguish glaucoma from other optic nerve diseases.
MS Optic Neuritis, MOG, NMO: The optic nerve is encased in a substance called myelin, much like the insulating wrap around an electrical wire. Optic neuritis is an inflammatory process, perhaps viral induced causes loss of the myelin. Optic neuritis typically affects patients less than 45 years of age. Vision loss occurs over hours to days, and is usually associated with pain on eye movement. The optic nerve inflammation is often located behind the eyeball, such that the front of the optic nerve, visible to the doctor in the office initially appears normal. In the vast majority of cases, vision will recover well without treatment although patients may notice persistent fading of colours and decreased sensitivity in poor contrast environments (e.g. foggy days). Optic neuritis may be associated with multiple sclerosis (MS). The MRI scan can help predct which optic neuritis patients have the greatest risk of developing MS. If many areas of demyelination (white matter plaques) are seen on MRI of the brain, the risk of MS is higher.
- The ten-year risk of developing clinically definite MS following a single episode of optic neuritis was 38% for the entire ONTT study group; the twelve-year risk was 40%. Most of those who developed MS did so within the first five years after the initial episode of optic neuritis.
- The strongest predictor of MS in the study group was the presence of brain lesions on MRI at the time of the episode of optic neuritis. Within the study group, patients with at least one brain lesion on MRI at the time of the optic neuritis episode had a 56% risk of developing MS within 10 years, while those with no brain lesions had only a 22% risk of developing MS within 10 years.
Although vision tends to recover well without treatment in optic neuritis, intravenous steroids and interferon treatment are thought to decrease the risk and severity of MS. Oral steroids at conventional doses (e.g. prednisone 60 mg) are not recommended for treatment unless preceded by intravenous steroids.
If the MRI is negative, but the patient has myelitis symptoms (arm or leg weakness, numbness or tingling, bladder or bowel dysfunction), or if the patient has intractable hiccups, unexplained nausea and vomiting, or symptomatic narcolepsy, neuromyelitis optica is a possibility. NEUROMYELITIS OPTICA (optic neuritis and myelitis) differs from MS by the presence of IgG autoantibody that binds to the protein Aquaporin 4. Intravenous steroids, plasma exchange and rituximab may be of help.
MOG (myelin oligodendrocyte glycoprotein) is NMO-like but not usually as severe. MOG often recurs, but the vision prognosis in MOG is better than NMO.
Atypical presentations of optic neuritis in older, non-Caucasian patients, the MRI findings of bilateral longitudinal enhancement, shaggy enhancement or perineuritis may also suggest NMO/MOG.
|Neuromyelitis optica spectrum disorder: AQP4 AB
|Myelin oligodendrocyte glycoprotein antibody associated disease: MOG Ab
|Bilateral vision involvement
|High dose steroids + plasma exchange
|High dose steroids
e.g. rituximab, eculizumab, inebilizumab, satralizumab
|If steroid dependent or relapse: IVIg or tocilizumab
?Satralizumab ? rozanolixizumab
Red flags to be considered before making a diagnosis of NMOSD (modified from Wingerchuk et al. 2015])
|Clinical and laboratory features
Progressive overall clinical course (neurologic deterioration unrelated to attacks; consider MS)
Time to attack nadir < 4 h (consider ischemia/infarction) or continual worsening for > 4 weeks from attack onset (consider sarcoidosis or neoplasm)
Partial TM, especially when not associated with LETM MRI lesion (consider MS)
AQP4-IgG positivity only in the CSF, not in the serum (can be true positive in very rare cases; e.g., if serum testing is hampered by strong background staining, or shortly after PLEX; always consider retesting of serum and CSF in an alternative assay)
AQP4-IgM and/or AQP4-IgA positive, but AQP4-IgG negative (clinical significance unknown; not sufficient for making a diagnosis of seropositive NMOSD)
“Double positivity” for AQP4-IgG and MOG-IgG (extremely rare/implausible; repetition of both tests recommended in all cases)
Presence of CSF-restricted OCB (present in ≤ 20% of cases of NMO vs > 90% of MS [lower in Asian and other populations])
Presence of a bi- or trispecific MRZ reaction (present in around 67% of MS patients, virtually absent in NMOSD)
Brain imaging features (T2-weighted MRI) suggestive of MS (MS-typical): Lesions with orientation perpendicular to a lateral ventricular surface (Dawson fingers), or lesions adjacent to lateral ventricle in the inferior temporal lobe, or juxtacortical lesions involving subcortical U-fibers, or cortical lesions
Spinal cord characteristics more suggestive of MS than NMOSD: Lesions < 3 complete vertebral segments (sagittal T2), or lesions located predominantly (> 70%) in the peripheral cord (axial T2), or diffuse, indistinct signal change (T2, seen with longstanding or progressive MS)
Lesions with persistent (> 3 months) Gd enhancement (suggestive neither of NMOSD nor MS) or persistent Gd enhancement despite immunotherapy (consider tumor/lymphoma or vascular malformation)
Brain linear perivascular radial Gd enhancement (consider GFAP-IgG-associated astrocytopathy and, possibly, neurosarcoidosis, vasculitis, lymphoma)
Cancer, established or with suggestive clinical, radiologic, or laboratory findings thereof; consider also lymphoma or paraneoplastic disease (e.g., CV2/CRMP5-associated optic neuropathy  and myelopathy, or anti-Ma-associated diencephalic syndrome)
Chronic infection, established or with suggestive findings thereof (e.g., HIV, syphilis, Tb)
ACE angiotensin-converting enzyme, CSF cerebrospinal fluid, IL2R interleukin-2 receptor, LETM longitudinally extensive transverse myelitis, MRZ measles/rubella/zoster virus reaction, i.e., intrathecally produced antibodies (positive antibody index) against at least two of these three viral agents, MS multiple sclerosis, OCB oligoclonal bands, PLEX plasma exchange, Tb tuberculosis, TM transverse myelitis
PSEUDOTUMOR CEREBRI (PTC / Idiopathic Intracranial Hypertension) PTC is a high pressure inside the brain that mimics a brain tumor. A normal MRI (or CT scan) of the brain is required to make a diagnosis. Lumbar puncture (needle in the spinal fluid space to withdraw fluid) is also required to exclue an infection of the fluid bathing the brain (cerebrospinal fluid), and to measure the intracranial pressure. High pressure in the head causes the normal nutrient flow in the optic nerve to back up and the optic nerve becomes swollen. Patients with PTC are usually obese. The increased fat increases the pressure in the chest cavity and impedes fluid drainage from the brain, causing increased pressure in the head. Weight loss is the cure for PTC in obese patients. Excess intake of carrots or liver, and certain medications such as tetracycline, excess vitamin A may induce PTC.
If the head pressure his high enough to damage the optic nerves, treatment may be required. Medications including acetazolamide (diamox) will help protect the optic nerves until the patient can lose weight. If medications are insufficient, and significant optic nerve damage is occurring, an optic nerve sheath decompression surgery may be required. During this procedure openings are made in the tissue sheath (well beyond the myelin) that surrounds the optic nerve, allowing release of the cerebrospinal fluid bathing the optic nerve and brain. To assist in weight loss, laparoscopic banding of the stomach can be considered.
If the veins of the head are clogged, a condition very similar to PTC may result. A special MRI called an MRV can delineate this condition.